The term “blood pressure” (BP) is defined as the pressure that is exerted upon the walls of arterial blood vessels due to blood circulating. BP is measured in millimeters of mercury (mm Hg) and is expressed in terms of the systolic pressure/diastolic pressure of the heart, e.g. 120/80 mm Hg. Systole is the part of the cardiac cycle when the ventricles contract and blood is forced outwards into the arteries. This results in the maximum pressure within the arterial blood stream occurring during each contraction, or beat, of the heart. Systole is followed by diastole, during which the atria dilate and the ventricles relax and refill with blood during the period between heartbeats. Diastole results in the minimum pressure within the arterial blood stream occurring during each heartbeat. A normal blood pressure value lies at or below 120/80 mm Hg, and is a result of sufficient arterial wall elasticity in the larger arteries and no fluctuation in the width of smaller blood vessels.
Abnormal blood pressure values are a fundamental diagnostic factor in the identification of conditions of the cardiovascular system, and are also indicative of endocrine and/or neurological disorders. Considering the effects of abnormal blood pressure vary from acute and potentially dangerous symptoms such as dizziness and/or fainting to chronic and life-threatening end-organ cardiac and renal damage, all effects of abnormal blood pressure levels are significant.
In 2014, approximately 22% of adults aged 18 and over had elevated blood pressure levels, or hypertension, globally. In the USA alone, approximately 29% of adults suffer from hypertension, of which only about 50% manage the condition effectively. At present, hypertension is the dominant cause of stroke and kidney failure and is part of a greater disease cluster continually accompanied by obesity, diabetes, kidney disease or many other co-existing problems involving lifestyle and/or genetics. Since high blood pressure is often not associated with noticeable symptoms, one in five adult individuals afflicted is unaware of it, with the cost of the condition to the United States amounting to roughly US$46 billion yearly. In 2013, more than three hundred sixty thousand deaths with high blood pressure as the principal or participating cause were recorded. Therefore, early detection, before high blood pressure leads to serious conditions, is essential.
Notwithstanding the fact that a currently used method for the accurate, direct, and continuous measurement of blood pressure exists, the method is invasive (it entails the use of an intravascular canula needle) and limited (potential complications such as thrombosis, bleeding and infection can arise). Also, for most individuals, obtaining a blood pressure reading with subsequent diagnosis necessitates a doctor's or clinic appointment, which can be time-consuming, costly and/or logistically demanding (for example in rural areas).
BP can be measured from different locations on or within the body, as well as different arteries, the methods varying in accuracy and feasibility. Reasons for utilizing different locations vary from accuracy of the method used on a specific artery, accessibility of an artery (for example, patients who are undergoing cardiac catheterization surgery are the only candidates for the most accurate, yet most invasive method, which involves measuring BP from the aortic root), as well as the type of equipment to which a clinic/hospital/medical officer has access. Currently, the most accurate non-invasive method is to measure brachial blood pressure (bBP). However, as bBP involves placing an inflatable cuff on the upper arm, it is not suitable for individuals who are sensitive to pressure and discomfort, such as the elderly, or persons with wounds or skin ailments in the area.
An alternative method, which is non-invasive and poses no pain or discomfort, is to perform tonometry of the radial artery (RA). The RA runs distally on the anterior part of the forearm, with the radial pulse measured from the wrist, in front of the distal end of the radius, where the RA lies superficially. Tonometry entails the use of a strain gauge pressure sensor exerting mild pressure over an artery. Subsequently, the artery is partially flattened and the arterial pressure is transmitted from the artery to the sensor, after which signal processing takes place to produce a digital readout.
Low-frequency arterial pressure fluctuations, termed Mayer waves, also occur due to sympathetic nervous system activity. Oscillations, or vibrations, in pressure receptor and chemo receptor reflex control systems generate these waves in arterial BP. Mayer waves occur spontaneously as a result of oscillation of the sympathetic vasomotor tone, and are detected through the application of spectral techniques to simultaneously recorded arterial pressure and efferent sympathetic nervous activity. It is speculated that Mayer waves trigger the release of endothelium-derived nitric oxide through cyclic changes in vascular shear stress, which could be beneficial to end organ function. Mayer waves can be measured by means of either tonometry, a photoplethysmography (PPG) sensor, or both. The short-term changes in blood volume are translated into pulse rate, and using tonometry in combination with PPG data mediates the filtering of the pressure wave signal for greatly enhanced accuracy and signal clarity after signal processing.
Two currently used gold standard measurements for BP exist. However, the first method is accurate, yet invasive, while the second method is non-invasive, yet less accurate. The first method entails direct measurement of aortic root pressures by passing a pressure transducer connected to a catheter directly into the aortic root at the time of cardiac catheterization. However, due to the high level of invasiveness of this method, it is not suited for routine clinical practice. The second method entails analysis of the radial artery waveform, obtained by non-invasive tonometry. The radial waveform is usually calibrated to bBP, measured using a brachial cuff and oscillometric devices, thereby generating a calibrated radial artery pressure waveform. However, this method presents challenges regarding a) accuracy, due to the phenomenon of white-coat hypertension and b) continuity, as the patient has to schedule an appointment to have BP measured. Moreover, during the implementation of both of the gold standard BP measuring methods, it is imperative that the subject remain still.
The inventors hereby recognized that the existing mechanisms used to measure BP are exclusive with regards to accuracy and/or invasiveness and/or discomfort to the user. Therefore, a strong need exists for a mechanism to measure ambulatory BP, i.e. to measure BP as the subject moves around, executing normal daily activities, in a non-invasive, accurate and continuous manner, simultaneously. Further, such mechanism needs to be non-invasiveness, accurate and continuous) for determining ambulatory BP.